Fig.1 Venny diagram of the constituent target of MEMS and AGA target

Fig.2 Protein-protein interaction network

Fig.3 The TCM-active components-drug targets network Rectangles represent the intersection targets of drugs and diseases, triangles represent the core active components of drugs, rhombuses represent the categories of traditional Chinese medicine, and concave quadrilaterals represent the common active components of drugs.

Fig.4 GO enrichment analysis bar diagram

Fig.5 KEGG enrichment analysis diagram

Fig.6 Molecular docking binding energy heat map (kcal/mol)

Fig.7 molecular docking diagram A,B: docking diagram of beta-sitosterol and target TNF; C,D: docking diagram of stigmasterol and target TNF.

Fig.8 Conformational stability analysis of TNF in complex with β-sitosterol or stigmasterol A-C: RMSD, RMSF, and Rg profiles of the TNF-β-sitosterol complex; D-F: corresponding profiles of the TNF-stigmasterol complex.

Fig.9 Hydrogen bonding and binding free energy analysis A,B: number of hydrogen bonds in the TNF-β-sitosterol and TNF-stigmasterol complexes, respectively. C,D: binding free energy decomposition. E,F: per-residue energy contributions for each complex.

Fig.10 The free energy morphology of TNF-β-sitosterol and TNF-stigmasterol complexes A: TNF-β-sitosterol; B: TNF-stigmasterol.

Fig.11 Effects of MEMS on ankle joint swelling, toe volume swelling, gait score, and inflammatory index in AGA rats A: ankle swelling before and 12 h after MSU injection; B: comparison of the degree of right posterior ankle joint swelling, the degree of toe volume ankle swelling, gait assessment score and Inflammatory index in rats of different group ($ \overline{x} $±s, n=6). bP<0.05, cP<0.01, compared with model group; eP<0.05, compared with EMS group.

Fig.12 Results of various indexes in rats ($ \overline{x} $±s, n=6) A: TNF-α; B: IL-1β; C: IL-6; D: IL-17; E: SOD; F: GSH; G: MDA. bP<0.05, cP<0.01, compared with control group; eP<0.05, fP<0.01, compared with Model group; hP<0.05, compared with EMS group.

Fig.13 HE staining of synovial tissues in rat ankle joints across experimental groups ($ \overline{x} $±s, n=6) The representative image of HE staining in synovial tissue (Scale bar=100 μm); the histological quantitative score of synovial tissue sections was average±SD. cP<0.01, compared with control group; eP<0.05, fP<0.01, compared with model group.

Fig.14 The expression levels of NLRP3 and STAT3 protein in ankle joint tissue of rats ($ \overline{x} $±s, n=6) A: STAT3 protein expression; B: NLRP3 protein expression; C: electrophoresis of STAT3 and NLRP3 proteins. cP<0.01, compared with control group; fP<0.01, compared with model group; iP<0.01, compared with EMS group.